Lithium and tamoxifen modulate cellular plasticity cascades in animal model of mania
In: Journal of psychopharmacology (Oxford), Jg. 26 (2012), Heft 12, S. 1594-1604
Online
academicJournal
- print; 11; 1 p.1/4
Zugriff:
Lithium (Li) is the main mood stabilizer and acts on multiple biochemical targets, leading to neuronal plasticity. Several clinical studies have shown that tamoxifen (TMX) - a protein kinase C (PKC) inhibitor - has been effective in treating acute mania. The present study aims to evaluate the effects of TMX on biochemical targets of Li, such as glycogen synthase kinase-3β (GSK-3β), PKC, PKA, CREB, BDNF and NGF, in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were treated with d-AMPH (2mg/kg, once a day) or saline (Sal; NaCl 0.9%, w/v), Li (47.5 mg/kg, intraperitoneally (i.p.), twice a day) or TMX (1 mg/kg i.p., twice a day) or Sal in protocols of reversion and prevention treatment. Locomotor behavior was assessed using the open-field task, and protein levels were measured by immunoblot. Li and TMX reversed and prevented d-AMPH-induced hyperactivity. Western blot showed that d-AMPH significantly increased GSK-3 and PKC levels, and decreased pGSK-3, PKA, NGF, BDNF and CREB levels in the structures analyzed. Li and TMX were able to prevent and reverse these changes induced by d-AMPH in most structures evaluated. The present study demonstrated that the PKC inhibitor modulates the alterations in the behavior, neurotrophic and apoptosis pathway induced by d-AMPH, reinforcing the need for more studies of PKC as a possible target for treatment of bipolar disorder.
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Lithium and tamoxifen modulate cellular plasticity cascades in animal model of mania
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Autor/in / Beteiligte Person: | CECHINEL-RECCO, Kelen ; VALVASSORI, Samira S ; VARELA, Roger B ; RESENDE, Wilson R ; ARENT, Camila O ; VITTO, Marcelo F ; LUZ, Gabrielle ; DE SOUZA, Claudio T ; QUEVEDO, Joao |
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Zeitschrift: | Journal of psychopharmacology (Oxford), Jg. 26 (2012), Heft 12, S. 1594-1604 |
Veröffentlichung: | London: Sage Publications, 2012 |
Medientyp: | academicJournal |
Umfang: | print; 11; 1 p.1/4 |
ISSN: | 0269-8811 (print) |
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